Search Results (136)

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

Osteoclasts, which are derived from myeloid precursors, are essential for physiologic bone remodeling but also mediate pathological bone loss in inflammatory diseases such as periodontitis and rheumatoid arthritis. Lysine-specific demethylase (LSD1/KDM1A) is a histone demethylase that modulates the chromatin landscape via demethylation of H3K4me1/2 and H3K9me1/2, thereby regulating the expression of genes essential for deciding cell fate. We previously demonstrated that myeloid-specific deletion of LSD1 (LSD1LysM-Cre) disrupts osteoclast differentiation, leading to enhanced BV/TV under physiological conditions. In this study, we show that LSD1LysM-Cre female mice are similarly resistant to inflammatory bone loss in both ligature-induced periodontitis and K/BxN serum-transfer arthritis models. Bulk RNA-seq of mandibular-derived preosteoclasts from LSD1LysM-Cre mice with ligature-induced periodontitis revealed the upregulation of genes involved in inflammation, lipid metabolism, and immune response. Notably, LSD1 deletion blocked osteoclastogenesis even under TGF-β and TNF co-stimulation, which is an alternative RANKL-independent differentiation pathway. Upregulation of Nlrp3, Hif1α, and Acod1 in LSD1LysM-Cre preosteoclasts suggests that LSD1 is essential for repressing inflammatory and metabolic programs that otherwise hinder osteoclast commitment. These findings establish LSD1 as a critical epigenetic gatekeeper integrating inflammatory and metabolic signals to regulate osteoclast differentiation and bone resorption. Therapeutic inhibition of LSD1 may selectively mitigate inflammatory bone loss while preserving physiological bone remodeling. Full article

Glehnia littoralis Fr. Schmidt ex Miq. has been cultivated in China for a long time and used as a medicinal plant called “Beishashen” in traditional Chinese medicine and has been traditionally known to have antibacterial and anti-inflammatory effects, but its direct role in periodontitis has not been known. Currently used periodontal treatments require long-term administration, which causes many side effects. Therefore, in this study, we evaluated the effects of G. littoralis extract (GLE) on periodontitis in an experimental periodontitis-induced in vitro and vivo model and understood its potential molecular mechanism. The effect of GLE on periodontitis in vitro was investigated using human periodontal ligament (HPDL) cells mediated by PG-LPS. Additionally, a ligature-induced periodontitis model and a PG-LPS-induced periodontal inflammation model were used to investigate the effect of GLE in vivo. In vitro study results showed that GLE down-regulated the increased inflammatory cytokines and mediators in HPDL cells stimulated with PG-LPS, and simultaneously down-regulated the levels of 11β-HSD1 and glucocorticoid receptor (GR), thereby alleviating periodontal inflammation. At the same time, it restored the lost osteoblast differentiation potential of HPDL cells. In addition, in an in vivo model representatively used for periodontitis research, the periodontal inflammation-alleviating effect and the effect of restoring or protecting damaged periodontal tissue were confirmed. GLE can be considered as a new periodontitis treatment agent through regulating 11β-HSD1. Full article

Periodontitis is an inflammatory disease that affects the periodontal supporting tissues. Its cardinal clinical manifestations encompass gingival inflammation, periodontal pocket formation, and alveolar bone resorption. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, is known for its anti-inflammatory and osseous-protective properties. Nonetheless, the impact of UA on periodontitis remains unknown. To investigate the preventive effect of UA, we employed a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 mouse macrophages, a receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model, and a ligature-induced periodontitis model in mice. The expression of inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) was analyzed to assess anti-inflammatory efficacy. Bone loss in mice with periodontitis was assessed through histological and imaging techniques, including haematoxylin and eosin staining to evaluate alveolar bone morphology, Masson’s trichrome staining to visualize collagen fiber distribution, and micro-computed tomography scanning to quantify bone structural parameters. Additionally, we investigated the underlying mechanisms by examining osteoclast activity through tartrate-resistant acid phosphatase staining and the expression levels of proteins RANKL and osteoprotegerin (OPG). We found that UA reduced IL-6 and TNF-α levels in vitro and in vivo, inhibited osteoclast differentiation, and decreased the RANKL/OPG ratio in periodontitis mice. Full article

Objective: This study aimed to evaluate the effects of local use of Brazilian Green Propolis (BGP), either as an ethanolic extract (the most common formulation) or incorporated into lipid-based nanostructures, as an adjuvant therapy for non-surgical periodontal treatment in managing experimental periodontitis (EP) in ovariectomized rats. Methods: Fifty-six female Wistar rats underwent bilateral ovariectomies. After 10 weeks, a cotton ligature was placed around the lower first molar and remained in place for two weeks to induce EP. The ligature was removed, and the rats were randomly assigned in the groups NLT (n = 14), SRP (n = 14), SRP-BGPee (n = 14), and SRP-BGPlns (n = 14). In the NLT group, no local treatment was performed. The SRP group received scaling and root planing (SRP), along with irrigation using a physiological saline solution. The SRP-BGPee group underwent SRP and irrigation with ethanolic extract of BGP. The SRP-BGPlns group underwent SRP and irrigation with BGP-loaded lipid nanostructure (BGPlns). Each group received one SRP session followed by four irrigation sessions with the specified solutions, which were conducted immediately after SRP and subsequently after 2, 4, and 6 days. Euthanasia was performed at 7 and 28 days following the removal of the ligatures. The hemimandibles were processed for the following analyses: microtomographic analysis; histological analysis; histometric analysis of the percentage of bone tissue in the furcation region (PBT); and immunohistochemical analysis for tartrate-resistant acid phosphatase activity (TRAP), transforming growth factor beta 1 (TGFβ1), and osteocalcin (OCN). Results: The SRP-BGPlns group demonstrated superior periodontal tissue repair, reduced alveolar bone loss, fewer TRAP-positive cells (at 7 days), and higher levels of immunolabeling for TGFβ1 (at both 7 and 28 days) and OCN (at 28 days) compared to the other experimental groups. Conclusions: The irrigation with BGP is an effective adjuvant therapy for non-surgical periodontal treatment in managing EP in ovariectomized rats. Its application in lipid-based nanostructures proved to be more effective than the ethanolic extract form. Full article

Background: Oral squamous cell carcinoma (OSCC), which accounts for over 90% of all oral malignancies, remains a major global health challenge due to its aggressive clinical course and poor prognosis. Periodontitis, a widespread chronic inflammatory condition affecting the supporting structures of the teeth, has increasingly been implicated as a potential risk factor for the development of various cancers. Emerging evidence suggests that microbial dysbiosis within the oral cavity may contribute to the creation of a pro-tumorigenic microenvironment, thereby promoting tumor initiation and progression. Nevertheless, the precise mechanisms linking periodontitis to OSCC, particularly through alterations in the oral microbiota, remain insufficiently understood. This article seeks to comprehensively analyze the association between periodontitis and OSCC and to elucidate the potential role of oral microbiota dysbiosis in mediating this relationship. Methods: In this study, a ligature-induced periodontitis model was established in C57BL/6J mice, and after two weeks, an OSCC model was introduced by the subcutaneous injection of SCC-7 cells to investigate the impact of periodontitis on OSCC progression. The effects of periodontitis on OSCC cell proliferation and invasion were assessed using scratch wound healing assays and CCK-8 proliferation assays. 16S rDNA high-throughput sequencing was conducted to profile the microbial communities present in the oral cavity and OSCC tissues, with particular emphasis on α-diversity indices (including Pielou’s evenness and Chao1 richness) and taxonomic composition at both the phylum and class levels. Furthermore, qPCR was utilized to assess the expression levels of cytokines in both periodontal and OSCC tissues, thereby elucidating the inflammatory milieu, potentially linking periodontitis to OSCC progression. Results: Our findings demonstrated that periodontitis significantly promoted OSCC growth and enhanced the invasive potential of OSCC cells. Microbial profiling revealed marked alterations in both the oral and OSCC microbiota, characterized by significant shifts in community composition and increased microbial diversity. Notably, these microbial changes exhibited consistent patterns between the oral cavity and the OSCC microenvironment, suggesting a potential mechanistic link between periodontitis-associated dysbiosis and OSCC progression. Consistently, qPCR analysis revealed elevated expression levels of IL-1β, IL-10, and IL-18 in both periodontal and OSCC tissues, providing evidence that the microbial alterations were accompanied by intensified inflammatory responses, which may contribute to OSCC progression. Conclusions: This study underscores the intricate interplay between periodontitis-induced microbial dysbiosis and the development of oral squamous cell carcinoma (OSCC). The findings suggest that periodontal inflammation, together with associated shifts in the oral microbiota, acts synergistically to drive OSCC progression. The elevated expression of cytokines further supports the role of a pro-inflammatory tumor microenvironment in mediating this interaction. These results offer important insights into the microbial and inflammatory mechanisms underlying the connection between periodontitis and OSCC, highlighting the critical role of maintaining periodontal health in the prevention and management of OSCC. Full article

This study aimed to develop and validate a dual murine model integrating a high-fat diet (HFD) and a single streptozotocin (STZ) dose to induce diabetes mellitus (DM), alongside periodontitis (Perio) induced by ligature placement and oral inoculation with Porphyromonas gingivalis (P. gingivalis). The goal was to mimic human pathological conditions, creating a physiologically relevant environment to study the interplay between DM and Perio. A total of 128 six-week-old male C57BL/6J mice were randomly divided into four groups: Control, DM, Perio, and DM-P. DM was induced by HFD and STZ injection, and Perio by ligature placement and P. gingivalis infection. Evaluations occurred at baseline and days 7, 14, and 21. Alveolar bone loss was assessed by micro-computed tomography, and inflammation was examined histologically. DM mice showed elevated glucose levels and insulin resistance. Perio and DM-P groups experienced significant bone loss compared with Control and DM groups. The morphometric analysis revealed abundant inflammatory cells and reduced collagen fibers in Perio and DM-P groups, especially at day 7. This dual murine model successfully replicated the key features of DM and Perio, maintaining overall health of the animals, and good tolerability by those subjects to the stress of both interventional procedures. Full article

Recognising the Bangla alphabet remains a significant challenge within the fields of computational linguistics and artificial intelligence, primarily due to the script’s inherent structural complexity and wide variability in writing styles. The Bangla script is characterised by intricate ligatures, overlapping diacritics, and visually similar graphemes, all of which complicate automated recognition tasks. Despite ongoing advancements in deep learning (DL), machine learning (ML), and image processing (IP), accurately identifying Bangla characters continues to be a demanding and unresolved issue. A key limitation lies in the absence of robust detection frameworks capable of accommodating the script’s complex visual patterns and nuances. To address this gap, we propose an enhanced object detection model based on the YOLOv11 architecture, incorporating a ResNet50 backbone for improved feature extraction. The YOLOv11 framework is particularly effective in capturing discriminative features from input images, enabling real-time detection with high precision. This is especially beneficial in overcoming challenges such as character overlap and stylistic diversity, which often hinder conventional recognition techniques. Our approach was evaluated on a custom dataset comprising 50 primary Bangla characters (including vowels and consonants) along with 10 numerical digits. The proposed model achieved a recognition confidence of 99.9%, markedly outperforming existing methods in terms of accuracy and robustness. This work underscores the potential of single-shot detection models for the recognition of complex scripts such as Bangla. Beyond its technical contributions, the model has practical implications in areas including the digitisation of historical documents, the development of educational tools, and the advancement of inclusive multilingual technologies. By effectively addressing the unique challenges posed by the Bangla script, this research contributes meaningfully to both computational linguistics and the preservation of linguistic heritage. Full article

Background/Objectives: Aging alters neutrophil functions, which may contribute to the progression and severity of periodontitis-related alveolar bone loss. Neutrophils play a key role in immune defense. However, the effects of aging on neutrophil functions and their contribution to periodontal disease remain unclear. This study examined age-related neutrophil dysfunction and its impact on periodontal bone loss. Methods: We used young (6 weeks old) and aged (18 months old) C57BL/6 mice to assess age-related neutrophil function. Neutrophil migration, superoxide production, phagocytic activity, and NETosis were evaluated. A peritonitis model and a ligature-induced periodontitis model were employed to investigate the relationship between neutrophil activity and alveolar bone loss. Results: Neutrophils from aged mice exhibited reduced migration toward pathogens compared to those from young mice. However, aged neutrophils showed increased superoxide production, elevated phagocytic activity, and enhanced NETosis. In the periodontitis models, these age-related neutrophil alterations coincided with accelerated alveolar bone loss in aged mice. Conclusions: The findings indicate that aging is linked to dysregulated neutrophil functions, characterized by excessive oxidative stress, heightened phagocytosis, and increased NETosis. These functional changes may contribute to immune dysregulation and tissue damage, thereby promoting age-related alveolar bone loss in periodontitis. Full article

Periodontitis is a common inflammatory disease that not only damages periodontal tissues but also induces systemic effects, including cardiac dysfunction. Mesenchymal stem cells (MSCs) offer regenerative potential due to their ability to differentiate, modulate immune responses, and secrete anti-inflammatory factors. However, the relative efficacy of local versus systemic MSC administration remains unclear. This study evaluated the therapeutic effects of adipose-derived MSCs (AD-MSCs) in a rat model of experimental periodontitis, comparing local and systemic administration. AD-MSCs were characterized based on morphology, surface marker expression, and differentiation potential. Ligature-induced periodontitis was established over 60 days, after which AD-MSCs (1 × 10⁶ cells) were administered either supraperiosteally (local group) or intravenously (systemic group). Periodontal regeneration was assessed through clinical, radiographic, and histopathological analyses, while cardiac function was evaluated using echocardiography and histopathological examinations. Results demonstrated that local AD-MSC administration provided superior therapeutic benefits compared to systemic delivery. Locally administered cells significantly enhanced bone regeneration, reduced inflammation, and improved periodontal tissue architecture. In contrast, systemic administration offered moderate benefits but was less effective in restoring periodontal integrity. Similarly, in the heart, local treatment resulted in greater improvements in systolic function, as indicated by enhanced ejection fraction and fractional shortening, along with reduced myocardial fibrosis. Although systemic administration also provided cardioprotective effects, diastolic dysfunction persisted in both treatment groups. In conclusion, local AD-MSC administration proved more effective in regenerating periodontal tissues and mitigating cardiac dysfunction, highlighting its potential as an optimized therapeutic strategy for periodontitis and its systemic complications. Full article

Background/Objectives: Gingivitis and dental caries are oral diseases resulting from bacterial accumulation in dental plaque, leading to inflammation, tissue destruction and the demineralization of tooth structures. Dioscorea communis, due to its anti-inflammatory and antimicrobial properties, could be a new treatment candidate. Methods: This study evaluated the preventive and therapeutic effect of a D. communis berry juice paste, formulated at 3% and 7% concentrations, on gingivitis and dental caries, in 55 male SKH-hr2 hairless mice. Gingivitis and dental caries were induced by ligation of the upper left incisor and the paste was applied topically three times daily, five days a week. Treatment efficacy was assessed through clinical examinations, photo-documentation, histopathological analysis and FT-IR spectroscopy. Results/Conclusions: Preventive administration of D. communis 7% significantly delayed disease onset, while therapeutic effects on established conditions were limited. Both concentrations were non-toxic to gingival tissues and dental structures. Full article

The pathological mechanisms underlying the ligature mark in hanging involve the skin layers and an ischemic mechanism. The apoptotic process develops whenever ischemic mechanisms affect the dermal and epidermal layers. Effector caspase-3 appears to play a crucial role in both acute and chronic pressure-induced skin ischemia. The aim of this study is to identify the role of caspase-3 as a marker of supravitality in the diagnosis of premortem hanging. Skin samples from ligature marks in hanging cases were collected to investigate this apoptotic process. The caspase-3 levels in compressed skin were significantly higher compared to those found in healthy skin (p < 0.005). The apoptotic process in ischemic epidermal cells begins with stable mechanical stress, as seen in the hanging model. Caspase-3 expression seems to vary from minutes after the initial stress input. Caspase-3 activation is an ATP-dependent process and can only occur if the victim was alive before the pressure was applied. Caspase-3 is a reliable marker of supravitality in ligature marks in premortem hanging cases. Full article

We investigated the antimicrobial properties and effects on bone resorption of Brazilian organic honeydew (OHD) from the Bracatinga tree (Mimosa scabrella Benth.), a rare honey certified with Denomination of Origin, using a periodontal disease model. Antibiofilm activity was assessed using a subgingival biofilm adhered to the Calgary device. Biofilms were treated with OHD, chlorhexidine (0.12%), or a vehicle twice daily for 1 min starting on day 3, at concentrations of 2× and 10× the minimum inhibitory concentration (MIC). We employed a ligature-induced chronic periodontal disease model and challenged it with Porphyromonas gingivalis in C57BL/6 mice. The chemical profile of OHD was analyzed using LC-ESI-IT-MS/MS. Results were evaluated by measuring bone loss and microbial composition of the ligature biofilm through DNA–DNA hybridization. OHD demonstrated significant activity against P. gingivalis (MIC 4%, MBC 6%) and reduced biofilm viability by 80% in vitro. In vivo, OHD decreased microbial populations and decreased bone loss associated with periodontal disease. Chemical analysis identified seven compounds in OHD, including five flavonoids and two lignans. This Brazilian honeydew from the Atlantic Forest exhibits strong antimicrobial properties and potential as a functional food for oral health, offering a promising alternative for the control and prevention of periodontal disease. Full article

The occurrence and severity of periodontitis (PD) tend to increase with age, and yet the underlying mechanisms remain unclear. Immune senescence is known to be triggered in mice and humans as they age. Experimental PD in mice has been shown to induce senescence biomarkers p16 ^INK4a and p21, dysfunction of antigen-presenting cells (APCs), and activation of the senescence-associated secretory phenotype (SASP). However, the causal links of senescence to experimental PD are not yet established. This study aims to elucidate the role of senescence in experimental PD at a causal level. The P16-3MR mouse model harbors the p16^INK4a (Cdkn2a) promoter, driving in vivo expression of synthetic Renilla luciferase, monomeric red fluorescent protein (mRFP), and herpes simplex virus-1 thymidine kinase (HSV-TK). This facilitates in vivo identification of p16 ^INK4a activation at the cellular level and the consequences of selective elimination of p16^INK4a-positive cells by ganciclovir (GCV) treatment. Mice were treated with/without GCV for two weeks during ligature-induced PD. In vivo bioluminescence imaging quantified p16^INK4a activation, while Western blot and immunofluorescence analyses assessed key senescence and inflammatory markers (p16, p21, p53, Cyclin D1, p-H2A.X, IL17, and IL1β). Alveolar bone volume was analyzed by micro-CT and histomorphometry. Our findings demonstrate that clearance of senescent cells in mice subjected to experimental PD alleviates inflammation and mitigates bone loss. These results suggest a causal role for senescence in PD pathology, raising the future prospect of senolytic agents for therapeutic intervention in PD. Full article

Background/Objectives: As non-thermal atmospheric pressure plasma (NTP) is known to have advantages in application in the medical field, we consider its applicability to periodontitis, a representative chronic inflammatory disease. The purpose of this study was to evaluate the effect of NTP in inhibiting the progression of periodontitis in a rat model when additionally used in scaling and root planing (SRP). Methods: To induce experimental periodontitis in 20 rats, ligatures were placed in the maxillary second molar and lipopolysaccharide from Porphyromonas gingivalis was injected around the teeth. Then, NTP treatment was performed for 2 or 5 min, together with scaling and root planing (SRP). To evaluate alveolar bone loss, micro-computed tomography (micro-CT) analysis and hematoxylin–eosin (H-E) staining were performed. Tartrate-resistant acid phosphatase (TRAP) analysis was performed to compare the number of osteoclasts, while immunohistochemistry (IHC) analysis was performed to determine the expression levels of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG). Enzyme-linked immunosorbent assay (ELISA) analysis was performed for the detection of cytokines (TNF-α, IL-1β, and IL-10) in tissues and sera. Results: When SRP was combined with NTP, alveolar bone loss was decreased, the number of osteoclasts and RANKL expression were decreased, OPG expression was increased, and pro-inflammatory cytokine (TNF-α and IL-1β) levels were significantly decreased. Compared with the NTP treatment for 2 min, when treated for 5 min, less alveolar bone loss, fewer osteoclasts, a lower RANKL expression level, and a higher OPG expression level were observed. Conclusions: This study evaluated the adjunctive treatment effect of NTP in periodontitis-induced rats. Based on the results of this study, we suggest that supplemental NTP treatment may be a good option for non-surgical periodontal treatment; however, further studies are needed to elucidate the mechanism through which NTP suppresses periodontal inflammation. Full article